Inhalation is the primary entry route for agents causing environmental, occupational and infectious disease. Pulmonary macrophages are the first line of defense for the respiratory surfaces of the lungs, and these cells ingest deposited particles. Inhaled dusts comprise a greater variety of organic and inorganic materials than seen by macrophages in other body compartments. We will investigate how the physical chemistry of the target particle influences endocytosis by pulmonary macrophages. The influence of the alveolar micro-environment and putative opsonins in modulating particle uptake will be examined. We will measure the effect of loading particles with chemotaxins on efficiency of uptake. We have developed in vivo and in vitro systems for quantifying the phagocytic function of pulmonary macrophages, and we now propose to use both assay systems for the examination of these variables. The in vivo uptake of deposited aerosols will be measured using fluorescently-labelled particles and a cytofluorograph to measure phagocytosis on a cell-by-cell basis. These results will be compared to in vitro phagocytosis of the same particles when incubated in suspension with macrophages recovered by lavage. The data on how particle properties inhibit or accelerate macrophage uptake can be used to help understand the pulmonary phagocyte response when challenged by inhaled ingents. The comparison of phagocytosis measured in vivo and in vitro will identify whether effects on phagocytosis are due to direct action on lung macrophages or reflect alterations in the alveolar micro-environment.